Structural Brain and Spinal Cord Signature of Spinocerebellar Ataxia 27B: A Multisite MRI-Based Study.

Abstract

BACKGROUND: SCA27B is a recently described ataxia, the precise anatomical basis of which remains unclear.

OBJECTIVE: The goal was to characterize the structural brain and spinal cord magnetic resonance imaging (MRI) signature of spinocerebellar ataxia 27B (SCA27B) using multimodal quantitative imaging.

METHODS: In this cross-sectional, multisite study, 28 genetically confirmed SCA27B patients underwent standardized 3 T brain and cervical spinal cord MRI. A group of age- and sex-matched healthy controls was recruited at participating centers using harmonized acquisition protocols. Cerebral and cerebellar volumetry were performed using FastSurfer and CerebNet, respectively. Diffusion tensor imaging was used to assess microstructural integrity in supratentorial white matter. Spinal cord gray and white matter areas were quantified at the cervical level using the SCT toolbox. Between-group comparisons were conducted using general linear models adjusted for age, sex, and site.

RESULTS: Mean age and Scale for the Assessment and Rating of Ataxia score of the SCA27B cohort were 68.7 ± 13.3 years and 10.5 ± 5.8 points. Compared with healthy controls, SCA27B patients exhibited significant volumetric reduction of the cerebellar vermis (lobules I to IV and vermis VIII). Diffusion analyses revealed widespread fractional anisotropy reduction in subcortical cerebral white matter, consistent with microstructural disruption. At the cervical spinal cord level, patients demonstrated significant gray matter area reduction, whereas white matter area was comparatively preserved. The combined pattern of vermian atrophy, supratentorial white matter diffusivity abnormalities, and spinal cord gray matter loss delineated a distinct structural signature of SCA27B.

CONCLUSION: SCA27B is associated with a structural phenotype extending beyond the cerebellum, involving subcortical white matter microstructure and spinal cord gray matter. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.